Phase II and Phase III MDMA-Assisted Therapy clinical trials

Phase II

Six Phase II randomized trials of MDMA-assisted psychotherapy for treatment of PTSD were conducted from 2004 to 2017. In Phase II studies, researchers administer the drug to a group of patients with a disease or condition. Typically involving a few hundred patients, these studies aren't large enough to show whether the drug will be beneficial. All six studies demonstrated acceptable safety and promising initial efficacy results. The FDA, after reviewing all available data in 2016, granted Breakthrough Therapy Designation to MDMA-AT in 2017 and approved the designs of two Phase III trials that started in 2018.

Phase III

A Phase III clinical trial tests the safety and how well a new treatment works compared with a standard treatment. In the first Phase 3 randomized, double-blind, placebo-controlled study of MDMA-assisted therapy, participants with severe PTSD were randomized to receive either manualized therapy with MDMA (n=46) or with placebo (n=44) at one of 15 study sites. Participants underwent three 8-hour experimental sessions spaced four weeks apart with a single divided dose of 80 to 180 mg MDMA or placebo, in addition to three preparatory and nine integrative therapy sessions.

Eighteen weeks after the start of the study, participants in the MDMA condition showed a significant reduction in PTSD severity, as assessed by Clinician Administered PTSD Scale (CAPS-5) (mean change=-24.4, SD=11.6, n=42) compared to participants in the placebo group (mean change=-13.9, SD=11.5, n=37, d=0.91, p < .0001). At the primary endpoint, 67% of participants in the MDMA group no longer met diagnostic criteria for PTSD, compared with 32% of participants in the placebo group. Across the same time period, there was also a significant decrease in functional impairment, as assessed by Sheehan Disability Scale (SDS) scores in the MDMA group (mean change=-3.1, SD=2.6) compared to the placebo group (mean change=-2.0, SD=2.4, p=0.0116).

The results of this first Phase III trial of MDMA-assisted therapy in people with severe PTSD indicate that three sessions of MDMA-assisted therapy significantly reduced PTSD symptoms and functional impairment, compared to placebo. The effect size (d=0.91) shown in this study between MDMA-assisted therapy and placebo was larger than effect sizes shown for any other previously identified PTSD psychotherapy or pharmacotherapy.